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Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease

Tubulointerstitial fibrosis is a common feature of kidney disease. Histone deacetylase (HDAC) inhibitors have been reported to attenuate renal fibrosis progression. Here, we investigated the effect of CG200745, a novel HDAC inhibitor, on renal fibrosis development in a mouse model of unilateral uret...

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Autores principales: Choi, Hong Sang, Song, Ji Hong, Kim, In Jin, Joo, Soo Yeon, Eom, Gwang Hyeon, Kim, Inkyeom, Cha, Hyunju, Cho, Joong Myung, Ma, Seong Kwon, Kim, Soo Wan, Bae, Eun Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070546/
https://www.ncbi.nlm.nih.gov/pubmed/30068917
http://dx.doi.org/10.1038/s41598-018-30008-5
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author Choi, Hong Sang
Song, Ji Hong
Kim, In Jin
Joo, Soo Yeon
Eom, Gwang Hyeon
Kim, Inkyeom
Cha, Hyunju
Cho, Joong Myung
Ma, Seong Kwon
Kim, Soo Wan
Bae, Eun Hui
author_facet Choi, Hong Sang
Song, Ji Hong
Kim, In Jin
Joo, Soo Yeon
Eom, Gwang Hyeon
Kim, Inkyeom
Cha, Hyunju
Cho, Joong Myung
Ma, Seong Kwon
Kim, Soo Wan
Bae, Eun Hui
author_sort Choi, Hong Sang
collection PubMed
description Tubulointerstitial fibrosis is a common feature of kidney disease. Histone deacetylase (HDAC) inhibitors have been reported to attenuate renal fibrosis progression. Here, we investigated the effect of CG200745, a novel HDAC inhibitor, on renal fibrosis development in a mouse model of unilateral ureteral obstruction (UUO). To examine the effects of CG200745 on renal fibrosis in UUO, C57BL/6 J male mice were divided into three groups: control, UUO, and CG200745 (30 mg/kg/day)-treated UUO groups. CG 200745 was administered through drinking water for 1 week. Human proximal tubular epithelial (HK-2) cells were also treated with CG200745 (10 µM) with or without TGF-β (2 ng/mL). Seven days after UUO, plasma creatinine did not differ among the groups. However, plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were markedly increased in the UUO group, which were attenuated by CG200745 treatment. UUO kidneys developed marked fibrosis as indicated by collagen deposition and increased α-smooth muscle actin (SMA) and fibronectin expression. CG200745 treatment attenuated these fibrotic responses and suppressed UUO-induced production of transforming growth factor-beta1 (TGF-β) and phosphorylation of Smad-2/3. CG200745 treatment also attenuated UUO-induced inflammation as indicated by the expression of inflammatory markers. Furthermore, CG200745 attenuated phosphorylation of p38 mitogen-activated protein kinase in UUO kidneys. In HK-2 cells, TGF-β induced the expression of α-SMA and fibronectin, which were attenuated by CG200745 cotreatment. These results demonstrate that CG200745, a novel HDAC inhibitor, has a renoprotective effect by suppressing renal fibrosis and inflammation in a UUO mouse model.
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spelling pubmed-60705462018-08-06 Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease Choi, Hong Sang Song, Ji Hong Kim, In Jin Joo, Soo Yeon Eom, Gwang Hyeon Kim, Inkyeom Cha, Hyunju Cho, Joong Myung Ma, Seong Kwon Kim, Soo Wan Bae, Eun Hui Sci Rep Article Tubulointerstitial fibrosis is a common feature of kidney disease. Histone deacetylase (HDAC) inhibitors have been reported to attenuate renal fibrosis progression. Here, we investigated the effect of CG200745, a novel HDAC inhibitor, on renal fibrosis development in a mouse model of unilateral ureteral obstruction (UUO). To examine the effects of CG200745 on renal fibrosis in UUO, C57BL/6 J male mice were divided into three groups: control, UUO, and CG200745 (30 mg/kg/day)-treated UUO groups. CG 200745 was administered through drinking water for 1 week. Human proximal tubular epithelial (HK-2) cells were also treated with CG200745 (10 µM) with or without TGF-β (2 ng/mL). Seven days after UUO, plasma creatinine did not differ among the groups. However, plasma neutrophil gelatinase-associated lipocalin (NGAL) levels were markedly increased in the UUO group, which were attenuated by CG200745 treatment. UUO kidneys developed marked fibrosis as indicated by collagen deposition and increased α-smooth muscle actin (SMA) and fibronectin expression. CG200745 treatment attenuated these fibrotic responses and suppressed UUO-induced production of transforming growth factor-beta1 (TGF-β) and phosphorylation of Smad-2/3. CG200745 treatment also attenuated UUO-induced inflammation as indicated by the expression of inflammatory markers. Furthermore, CG200745 attenuated phosphorylation of p38 mitogen-activated protein kinase in UUO kidneys. In HK-2 cells, TGF-β induced the expression of α-SMA and fibronectin, which were attenuated by CG200745 cotreatment. These results demonstrate that CG200745, a novel HDAC inhibitor, has a renoprotective effect by suppressing renal fibrosis and inflammation in a UUO mouse model. Nature Publishing Group UK 2018-08-01 /pmc/articles/PMC6070546/ /pubmed/30068917 http://dx.doi.org/10.1038/s41598-018-30008-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Choi, Hong Sang
Song, Ji Hong
Kim, In Jin
Joo, Soo Yeon
Eom, Gwang Hyeon
Kim, Inkyeom
Cha, Hyunju
Cho, Joong Myung
Ma, Seong Kwon
Kim, Soo Wan
Bae, Eun Hui
Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
title Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
title_full Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
title_fullStr Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
title_full_unstemmed Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
title_short Histone deacetylase inhibitor, CG200745 attenuates renal fibrosis in obstructive kidney disease
title_sort histone deacetylase inhibitor, cg200745 attenuates renal fibrosis in obstructive kidney disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070546/
https://www.ncbi.nlm.nih.gov/pubmed/30068917
http://dx.doi.org/10.1038/s41598-018-30008-5
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